Gene delivery has been extensively explored as a promising therapeutic tool for treating genetic diseases or producing animal disease models. Due to the growing concern about the safety of viral vectors, non-viral gene delivery system was proposed as an alternative. Among those non-viral vectors that have been investigated, polyethylenimine (PEI) is one of the most widely used polymers. PEI forms polyplexes with DNA molecules due to the electrostatic interaction. After uptake by cells, PEI induces “proton sponge effect” and promotes the endosomal escaping of polyplexes.
Thus, PEI has been considered as a benchmark for non-viral vectors; however, the in vivo therapeutic application of PEI has been hampered due to several issues. First, the PEI/DNA polyplexes system is not compatible with serum, which is the main cause for low transfection efficiency. Second, PEI is cytotoxic and can cause cell death and possible organ damage if applied in vivo. Third, PEI as well as other non-viral vectors is much less efficient than viral vectors.
To decrease the cytotoxicity and further increase its transfection efficiency, PEI has been formulated with polysaccharide-based polyanions, such as hyaluronic acid. From our previous study, we found that the PEI/HA system did increase the transfection efficiency and decreased cytotoxicity; however, it was not resistant to the high concentration of serum which exists in in vivo conditions.
Thus, conventional non-viral gene delivery vectors are not compatible with serum, which hampers their in vivo applications. As such, a need exists for a non-viral gene delivery system (PoSH) which is compatible with serum.